In the leather dyeing process, anionic dyes are more suitable for coloring chrome-tanned leather compared to other tanning systems, especially organic tanning. Dye penetration and surface fixation depend on the charge of the dyes and the nature of the substrate, which leads to poor dye bath exhaustion and subpar fastness characteristics. Therefore, in this study, ionic liquid (imidazolium dihydrogen phosphate (IDP)) pretreatment was employed due to its superior ability to enhance the dye dispersion and make anionic dyes suitable for various types of tanned leather, including chrome, vegetable, and aluminum-silica tanning. Unlike conventional methods, ionic liquid pretreatment alters the tanned surface hydration layer, creates an ionic imbalance, and generates extra functional sites, causing dyes to adhere effectively to the leather. Molecular dynamics (MD) simulations of collagen in different proportions of ionic liquid and dye in an aqueous medium show that the collagen:IL:dye ratio of 1.0:0.5:0.5 in an aqueous medium is illustrated to be optimum in terms of performance compared to the conventional process because of the better dispersibility and diffusion of dye in the presence of an ionic liquid. Compared with the conventional dyeing process, ionic liquid pretreatment demonstrated enhanced dye uptake (5−24%) and uniform dyeing regardless of the nature of the tanned substrate. The minimal use of ionic liquid mitigates the negative effects caused by conventional auxiliaries and offers the potential for reusability in subsequent processes. Furthermore, a greener metrics evaluation (including ERF�excess reactant factor, RME�reaction mass efficiency, EF�environmental factor, and WWI�water waste intensity) confirms that ionic liquid pretreatment promotes leather dyeing in a more sustainable manner than the conventional system. EcoScale measurements also reveal that this innovative dyeing system utilizing an ionic liquid effectively addresses the environmental footprint associated with traditional dyeing processes.